Solid Lipid Nanoparticles for Dibucaine Sustained Release

Abstract

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72–89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers

“…The three types of NLC formulations developed in this study showed very good capacity to carry TTC, with %EE values ranging from 63.7 to 68.1% and %DL > 11 (Table 2 ), reflecting the strong partition of the non-ionized form of TTC in the lipid milieu 43 . Indeed, the encapsulation efficiency determined for TTC in these nanoparticles was in the range of those reported (> 55%) for other hydrophobic local anesthetics such as dibucaine, bupivacaine and ropivacaine 16 , 44 , 45 and higher (< 37%) than those observed in NLC with more hydrophilic agents such as lidocaine and prilocaine 8 . The drug loading capacity is another parameter that expresses the upload capacity of DDS (Eq.…”

Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration

“…The thermogram of CP and NPX exhibited a single endothermic peak at 55 °C and 157 °C, respectively, corresponding to their melting points 10,21 . For the NLC and NLC-NPX formulations a single endothermic transition was detected at 52 °C, related to the melting point of cetyl palmitate 22 .…”

“…Furthermore, calorimetric measurements revealed thermodynamic features of NLC-NPX formulation. The lower transition observed for the residual CP peak probably results from its interaction with the liquid lipids, decreasing the crystallinity of the nanoparticles core 22,40 . Moreover, the lack of the endothermic transition assigned for NPX in the NLC-NPX sample can be a sign of the solubilization of the NSAID in the nanoparticles (as pictured by the NTA data – Table S6).…”

Nanocarriers From Natural Lipids With In Vitro Activity Against Campylobacter jejuni

“…The long-term stability study is an essential test to ensure the shelf-life of novel formulations ( Barbosa et al., 2018 ). Then, the nanoparticle size (nm), PDI (particle size distribution), and Zeta potential (mV) values were followed over a year at 25°C ( Rodrigues da Silva et al., 2017 ).…”